A Phase III, Randomized, Open-Label, Multi-Center, Global Study of MEDI5752 as Sequential Therapy Versus Observation in Participants with Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma, Who Have Not Progressed Following Definitive Concurrent Chemoradiotherapy

PI: Prof.ssa Lisa Licitra 

The eVOLVE-HNSCC study is a global clinical trial evaluating the activity of Volrustomig (also known as MEDI5752) in patients with locally advanced, unresected squamous cell carcinoma of the head and neck, treated with definitive concurrent chemoradiotherapy (i.e., administered with curative intent). 

Volrustomig is a bispecific antibody, meaning it is a molecule that simultaneously binds to two different proteins in the body: PD-1 (Programmed Cell Death Protein 1) and CTLA-4 (Cytotoxic T-Lymphocyte-Associated Protein 4), both of which regulate the immune system’s response to cancer. 

This study, conducted in accordance with European regulations, is considered experimental because the investigational drug Volrustomig has not yet been approved by health authorities. 

Specifically, given the current lack of additional therapies after the completion of chemoradiotherapy, this trial proposes to evaluate the efficacy of Volrustomig compared to observation alone in patients who have completed concurrent chemoradiotherapy. By adding Volrustomig after chemoradiotherapy, the study aims to improve patient outcomes by reducing the risk of tumor recurrence (either locally or at distant sites) and improving progression-free survival and overall survival. 

Enrollment feasibility in the study depends on: patient characteristics (demographic data, cancer history, and comorbidities), laboratory tests, and radiological parameters, all of which will be assessed through specific screening tests before treatment begins. These tests will be conducted at this Institution according to clearly defined timelines. 

In Part I of the screening, analysis will be conducted on the tumor tissue and the biomarkers PD-L1 (Programmed Death-Ligand 1) and HPV (Human Papillomavirus), if the tumor originates in the oropharynx. These analyses may be performed on the stored biological sample, i.e., the biopsy taken before starting chemoradiotherapy. 

If PD-L1 positivity is confirmed (with a CPS score ≥ 1), Part II of the screening will begin. The study design includes: 

• Arm A: Active treatment with Volrustomig. The drug will be administered after completion of concurrent chemoradiotherapy and in the absence of disease progression. It will be given intravenously every 3 weeks for 12 months or until disease progression. 
• Arm B: Observation only for 12 months, during which the patient will not receive any medication but will be monitored clinically and through imaging tests. 

Assignment to one of the two arms will occur through a computerized process called randomization, meaning random assignment either to active treatment with Volrustomig or to observation, without any decision-making power by the investigator and/or the patient. 

If the assigned arm includes administration of the investigational drug Volrustomig, the patient will also be monitored for potential immune-mediated toxicities, which will be explained during the informed consent process prior to the start of the trial. The treatment may cause adverse events, some of which are already known, for which the researchers will propose symptomatic therapies and implement strategies to reduce their severity (e.g., dose reductions or treatment pauses). 

Treatment will continue for up to 12 months (or 18 administrations) and will be discontinued only in the event of disease progression, unacceptable toxicity, or— as is always the case in clinical trials — if the investigator and/or the patient decide to withdraw. In any case, the patient will continue to have access to medical care and will not forfeit any legal rights or entitled benefits. 

The study staff remains available for more detailed information (email: amo@istitutotumori.mi.it).